The cornea accounts for two-thirds of the refractive power of the human eye. This power can be altered by changing the corneal curvature or by varying the cornea's index of refraction. According to the National Center for Health Statistics, approximately 52% of the United States population wears some form of corrective lenses. While there have been significant advancements over the past decade in refractive surgery to correct myopia, hyperopia, and astigmatism, certain problems remain. Laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) have proven very effective in the correction of myopia, astigmatism, and low-moderate hyperopia. Principle limitations of these procedures are their lack of reversibility and limited efficacy in the correction of hyperopia and high myopia.
Recently, with FDA approval of a phakic intraocular lens (IOL) [Verisyse, Advanced Medical Optics Santa Ana, Calif.], there is a potentially improved means to treat high myopia. While these phakic IOLs provide excellent quality of vision to implanted myopes, they can be associated with severe intraocular complications such as endophthalmitis and corneal decompensation. Additionally, these IOLs are not as safe to implant in patients with hyperopia who tend to have shallow anterior chambers and are at increased risk for corneal damage from the implant.
These problems with current refractive surgical approaches have renewed interest in intracorneal implants (inlays) to treat hyperopia and high myopia. Implanting a lenticule in the cornea to correct refractive error is not a new idea. In 1949, Barraquer described implantation of 6 mm flint glass intracorneal lenses in a rabbit model. The corneas developed stromal necrosis and the lenses were extruded. Subsequent experiments by Barraquer using polymethylmethacrylate (PMMA) lenses had similar results. He concluded that limited metabolic exchanged across the synthetic onlay was incompatible with corneal viability. In 1967, Dohlman tested a hydrogel inlay made of glyceryl methacrylated in rabbits and cats. These water permeable implants enabled metabolic exchange and were better tolerated by the rabbit cornea; however, by 3 months, they were often extruded. In the cats there was excellent clinical biocompatibility and no extrusion. Other attempts at a synthetic inlay using colloidin, polypropylene, sialastic, and polysulfone were not well tolerated by the cornea, leading to loss of transparency.
Based on the initial promising results with hyrogel inlays, these materials have been the most exhaustively studied in animal models and more recently, in clinical trials. A microporous hydrogel formulation (Nutrapore®) has been incorporated in a corneal inlay (PermaVision®, Anamed Inc., Anaheim, Calif.) and implanted to correct hyperopia and high myopia. These inlays are 5.0 mm in diameter with a central thickness ranging from 25-60 μm. Their water content is 78% and the refractive index is similar to the cornea. Michieletto and co-workers reported on 10 hyperopes implanted with the PermaVision® lens using a microkeratome to create a corneal flap and securing the implant without sutures. While one inlay had to be removed due to decentration, no other eye lost best corrected visual acuity and the lenses appeared to be well tolerated for the 6 month follow up. Notably, no eye was operated that had more than 0.5 diopters of pre-operative astigmatism. Guell et al reported 6 hyperopic eyes implanted with a PermaVision® inlay. While all eyes were 20/40 or better at 12 months without correction, only 1 eye was 20/20 without correction. The authors concluded that predictability of inlay power “must be improved.” Werblin and co-workers reported use of different hydrogel inlay, the Permalens® (Alcon Labs, Fort Worth, Tex.), to correct high myopia. Inlays ranging from −10.00 to −15.00 diopters were implanted in 5 myopic patients. With a follow up of at least 18 months in all cases, corneal clarity was maintained, but as in the hyperopic inlays, power predictability was a significant issue. In fact, the mean post-operative refractive error was −5.7±2.1 diopters. While these pilot studies using hydrogel inlays for correction of hyperopia and high myopia establish general biocompatibility (some studies have shown cases of perilenticular inflammation or fibrosis), they do reveal the need for adjustability to maximize visual outcomes. Because it is impossible to predict the post-operative refractive error in patients after implantation, a means to post-operatively adjust inlay power would be desirable.
A significant limitation of current hydrogel inlays is their inability to address the important need for post-operative adjustability.
U.S. Pat. No. 4,264,155 (issued to Miyata) discloses soft contact lenses made from collagen gels to which water-soluble organic polyhydroxy polymers, e.g., mucopolysaccharides, polyvinyl alcohols and the like are added, followed by chemical cross-linking of the gels. The polyhydroxy polymeric additives are said to “surround” the strands of the collagen molecules to protect them against microbial degradation. No teaching or suggestion is made in U.S. Pat. No. 4,264,155 of possibly acylating collagen to produce ethylenically unsaturated or polymeric substituted collagen which could then be polymerized to form useful biomedical articles having high biological and tissue acceptability.
It is known e.g. from WO 95/13764 to provide corneal prostheses composed of porous polymeric material for correcting the optical properties of an eye or altering the appearance thereof. Corneal inlays are in general implanted into or onto the cornea of a mammal using surgical methods, for example by making an incision in the stromal tissue of the cornea to form a pocket into which the onlay is placed, and then closing the incision by suturing.
An alternative approach to correction of refractive error is placement of a corneal onlay. This has the advantages of being reversible, surgically simpler, and stable. The idea is that placement of the onlay on the Bowman's layer over the corneal stroma changes the corneal curvature thereby altering the refractive power of the cornea.
One method involves removing the corneal epithelial cell layers of the cornea by scraping, placing a synthetic lenticule directly onto and in intimate contact with the corneal tissue and holding it in place for a period of time which is sufficient for the epithelial cells to recover, grow over the implant and thus fix it in a persistent manner. The initial temporary fixation of the onlay on the cornea is accomplished by the use of a biocompatible glue such as a commercially available collagen- or fibrin-based two components glue. However said glues have not yet proven satisfactory mainly because of severe handling problems.
In view of these and other drawbacks, there is a need for improved materials for biomedical moldings, and in particular, corneal onlays.